Manmeet Ahluwalia, MD, Cleveland Clinic

The de-escalation of therapy helps avoid unnecessary toxicity from treatment in patients with brain cancer, explained Drs. Joshua K. Sabari and Manmeet Singh Ahluwalia.

Delving Into Brain Cancer Treatment Takeaways Following ASCO 2025

The de-escalation of therapy helps avoid unnecessary toxicity from treatment, making it an important consideration during the treatment of patients with brain cancer or metastases, Dr. Manmeet Singh Ahluwalia said during an interview with Dr. Joshua K. Sabari on the topic of the 

. Ahluwalia went on to highlight the emergence of antibody-drug conjugates and immunotherapy in across the therapeutic landscape, new drugs and approaches which help improve survival and neurologic function for patients, and pushing the envelope of treatment.

To kick off their conversation, Ahluwalia and Sabari began by highlighting the CATNON trial, a randomized, multicenter trial for patients with grade 3 gliomas being conducted by EORTC with U.S. cooperative group participation. The investigation aimed to understand if treatment with temozolomide chemotherapy provided patients with benefit when given concurrently with radiation versus after radiation.

According to Ahluwalia, investigators of the CATNON trial found that the concurrent treatment did not provide benefit, and that there was a clear benefit derived in patients who were treated with adjuvant therapy post-radiation

Moreover, Sabari and Ahluwalia went on to highlight the HER3-DXd antibody-drug conjugate to be used in patients with brain metastases from their lung and/or HER2-positive breast cancer. Ahluwalia explained that, of those treated with the investigational therapy, he trial reported a 30% intracranial response rate in patients with lung cancer brain metastases. Additionally, there was a 23% intracranial response rate for patients with brain metastases from their breast cancer.

Of the patients with leptomeningeal disease, 65% of patients survived three or more months, while 50% experienced benefit of 6 months or more. Overall, Ahluwalia said that the HER3-DXd agent provided intracranial activity in this difficult-to-treat patient population, including those with leptomeningeal disease.

Sabari is the editor in chief of CURE. He also serves as an assistant professor in the Department of Medicine at NYU Grossman School of Medicine and director of High Reliability Organization Initiatives at Perlmutter Cancer Center. Ahluwalia is a neuro-oncologist. He serves as the chief scientific officer, chief of medical oncology, deputy director and Fernandez Family Endowed Chair in Cancer Research at Baptist Health Miami Cancer Institute.

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The de-escalation of therapy helps avoid unnecessary toxicity from treatment in patients with brain cancer, explained Drs. Joshua K. Sabari and Manmeet Singh Ahluwalia.


I’m going to pose a question now to everyone. How can the medical team improve the care of patients with brain metastases? Perhaps we can start with having Ivy and Katie speak to that.

Patients need information. That’s probably the most important thing. When you’re diagnosed, everything is thrown at you. I think patients need to understand what brain metastasis means, how that can impact their lives, if they’re asymptomatic versus symptomatic, what the options are for treatment, both short term and possibly long term. That needs to be laid out to people in an easily understandable way up front. I also think patients need to understand what the ongoing management is going to be for brain metastases, how often they’ll be scanned, if you have certain symptoms, when you should bring that up and maybe recommend moving a scan up earlier. But basically, what it comes down to is increased information.

I agree. We’ll have Ralph, after Katie has a chance to speak, but that’s exactly what the ABTA [American Brain Tumor Association] survey results showed us, too. But Katie, do you want to add to that?

I agree with everything Ivy said, although I have already said I’m the patient who doesn’t want to hear all the worst-case scenarios. I don’t know how I would have responded if a doctor said, “Listen, I need you to be looking for these things,” because then I would be like, “Oh my god, I think that symptom happened to me last week, I think I have a brain tumor, I think you need to scan me right now.” But I think I’ve gotten a little bit better now that I’m seasoned at dealing with this.

Another thing that was shocking to me was, I’m not claustrophobic, I didn’t think I was, until I got a brain scan. That’s a very different scan. If you think, “Oh, I’ve done scans, I know what I’m doing,” and suddenly you’re going headfirst down a very narrow tube with a cage on your head, it’s terrifying. To this day, if I ever hear of someone having to go in for a brain scan, I’m always very careful with how I present information to other patients. But I always do say, “That one is a little harder for me, and I take a Valium for it.” I call that a cancer perquisite. But Nick has to drive me to those scans now because they still, to this day, I get a lot of anxiety around that particular scan.

 I think your experience is not a rarity, I think other patients have had similar experiences. Ralph, do you want to add to that?

Sure. I think you all know this very well, but patients and caregivers trust you and respect you. When you take the time to sit down and give them clinical trial treatment options, they listen, they absorb it. But it’s important that you also involve your team, your nurses, and your social workers, so that when they leave the office, they trust you, but sometimes they don’t fully understand everything that you have said. Having your support staff following up, working with them on clinical trials is important. Second, the survey shows how much they lean on, and want to know more about, organizations like the ABTA. You can trust us to work with them where they are and then afterward. People like Nick, who is a phenomenal caregiver, we can talk to him about whether he’s interested in being a mentor to others after he feels like Katie is at a place where he can give time to other caregivers.

 I completely agree, Ralph. Dr. Gondi, did you want to add to, how can we as a field improve the care of a patient with brain metastases?

As I listen to Ivy, Katie and Nick speak, it reminded me, at least in my clinical experience, that when systemic cancer goes to the brain, there are a lot of emotions, understandably, there’s a lot of fear, there’s a lot of confusion, consternation. And it’s not just on the patient’s perspective, but even some medical oncologists. What I’ve appreciated is that sometimes medical oncologists, as a brain tumor specialist, and I’m sure Dr. Brastianos, you probably do the same, I just say, “You know what, I’ll take care of the brain. Everything above the neck, I’m going to watch and keep an eye on, and everything below the neck, your systemic oncologist can keep an eye on it, and we’ll do it together.” That collaboration becomes useful. Just during this Zoom call, I’ve gotten a couple of texts from medical oncologists about patients we have, and I think that gives patients and their providers some sense of calm and comfort, that everything is taken care of up here, that we’re OK. If I have a headache, call that doctor who specializes in brain stuff and let him know, so that they can address it. I do think that there is tremendous opportunity to help and augment the care of patients and their providers, especially when we’re talking about the brain.

Of the two concepts I tried to cover, one is that the neurological team, whether they are a surgeon, radiation oncologist, or whatever, they have the knowledge and expertise pertaining to the brain and to the central nervous system. That team is bringing that expertise to help the medical oncologist treat the patient in a complete way. The second concept is that it’s a complicated world, and one specialist within the neuro field cannot handle all the problems of brain metastasis. It does require a whole team of a surgeon, oncologist, radiation, radiologist, and so on and so forth. Bringing all these together in the brain metastasis concept is a great advantage for patients.

 I completely agree. On that note, we can be providing more support to caregivers. Nick, you already alluded to that earlier, but tell us more about how we can help caregivers.

This morning was a good example, my first question to Kate was, “How are you doing?” I think that’s a nice question also to ask a caregiver, how are they doing. I think I would like to see more proactive support offered, and if you do need support, here are avenues you can use to find support and information. Then what do you need as well as a caregiver, what can we do to support you, because we’re here to help the patient. The more that we can be supported to be in a better place to help the patient, the better that could be for us. Even Ivy talked about how she was the patient, she looked after the kids. I’m sure while her husband was working, that was a huge impact on him, as much as there was when I had to go to Pittsburgh, change my schedule, and be there to support Katie in the hospital every day. It would be great for a little more attention to the caregiver, to make sure things are well there, because we’re here to help the patient, and we’re part of the overall story and on the journey together.

That’s so important, Nick, thanks for saying that. Again, thank you to Katie, Nick and Ivy for sharing these deeply personal journeys. We’re so inspired by your stories. Thank you, and we hope that you’ll continue to do well and respond to therapies. I think we’ve reached time. Thank you to everyone who participated in today’s 

® program. I want to thank Ivy and Katie for sharing your story, and my colleagues, Vinai Gondi, Ray Sawaya, Manmeet Ahluwalia, and of course, Ralph DeVitto, for this incredible discussion. To our viewing audience, we hope you found this presentation to be useful and we’ve provided you with practical information that you can discuss with your health care provider. Thank you so much, everyone.

Improving Outcomes for Patients With Brain Metastases

How do you define treatment success for Katie?

It’s a good question. I was thinking about that as I heard Ivy and Katie talking. I think one of the things that she talks about is living to old age, and she has a number, 89, that is like a targeted area for her. I think for us, to be able to enjoy our life and live our life. I’d love to grow old together. If we can do a treatment and get back to the closest sense of normality and to be able to, as Katie said, go traveling and see friends and family and enjoy our lives, I think that’s the most important thing for me and for us.

Another question for you. What are your thoughts or feelings when Katie does enroll in clinical trials?

I do feel that I’m part of the decision-making. Like the TIL [tumor-infiltrating lymphocyte] therapy, we did have a pamphlet for that, and I read through what the situation was with that. We had a couple of options before going into this clinical trial, one of them, embolization, which we’d done, and then TIL. And the doctor explained what the tools in the tool belt were to help, to a reference earlier on. I felt part of the decision-making and confident about the treatment options. I think clinical trials are very good for patients. As Katie explained earlier, the initial treatment option that we were offered right back when the cancer had metastasized wasn’t the best option. Clinical trials, if we could do something new that might have a huge impact on this type of cancer and prove successful for her, is very much something that I would advocate for.

I think this last treatment had the most disruption on Nick’s life of all of the treatments that I’ve had, because we bought a one-way ticket to Pittsburgh, Pennsylvania, at the beginning of September, and we didn’t know when we were coming home. We spent the whole summer, we’d go on walks with our dog every day, and we would talk about, “What does that look like for you, what does that look like for me?” There were a lot of logistics. We found an Airbnb, and Nick stayed there. We had a friend of a friend who lived in town, who lent him a monitor so he was able to set up and work, so that it wouldn’t disrupt his work. We found a chef who would deliver about four or five meals a week, so that he could pop those in the oven and not have to cook but eat a healthier meal than eating out every meal, so that he could get to the hospital every night and visit me before visiting hours ended. That trip was as much of an impact on me as it was on him, and he has always been so supportive and takes it as it comes and never complains.

As a caregiver, if I can avoid FMLA [taking unpaid leave through the Family and Medical Leave Act], that’s the biggest success, to be able to continue my life while supporting Katie in Pittsburgh. That was starting work at 10 am for the times that we were here, working through to 6:30 pm, chucking food into the oven, and then straight to the hospital after I’d scarfed it down, basically. Whatever I could do to try to live a normal life for myself and for her, allows me to be the best caregiver I can be for her, too.

That’s incredible, Nick. It sounds like you’re such an amazing support for Katie.

A Caregiver’s Perspective on Treatment Success

Ivy and Katie, do you feel supported during your treatment by your medical team, your loved ones? You’ve already answered the question, that you both have amazing support networks. But tell us more about whether you feel supported by the community around you?

Yes, I really do feel supported. My oncologist and her staff are absolutely fantastic and if I have any questions, I know exactly how to reach out and get answers. I have a great group of friends here in my community who, along with me, have learned a lot about lung cancer over the past seven years, including the fact that anyone can get lung cancer, you just need to have lungs, which none of us knew before I was diagnosed.

I would say that I feel very supported by pretty much everyone in my life, and I am very grateful for that. Like Katie said before, I too feel that having cancer has changed my life. I also focus more on the present and try not to sweat the little things. It’s even changed my whole career focus because I’m a full-time patient advocate now, and I help others. It really has changed my life in many ways, and as a result of having had good support myself, I feel that I can support other people and help advocate for them as well.

Both of your stories are so moving, I have to say. Nick, you’ve been waiting patiently, thank you. Let’s turn our attention now to you as a caregiver. Again, thank you so much for joining us today and for being so supportive of Katie. How much of an effect did you have on treatment decision-making through this whole process?

Thanks for inviting me to speak today and to represent caregivers and to share our story and my story. Treatment diagnosis, I think Katie explained a little bit about it. It happened quickly when it spread to the brain. I was at work when she had a lot of the calls with the doctors and the results were shared and pieces like that. We knew that there were problems going on, so I was relieved that we’d found what the situation was. We had a lot of trust in the oncologist as well. I think building rapport is very important and we had that trust in him, Dr. Gonzalez. It really helped when he said, “Hey, this is what we’re going to be doing and why we’re going to be doing it, and we need to move quickly to do this.” For me, I felt at ease, that, OK, there’s a brain tumor, but here’s the next step with that.

Also, we’re very lucky to have Katie’s dad, who is a doctor. She refers to him as her agent in this as well. He’s always a good person to reference to and see how he is responding and reacting to what we’re doing. I can tell if he’s looking for different options, whether he’s worried about it as well. I feel if he’s like, “Yes, that’s fine, we’re going to do this,” then obviously that reassures me, and then I can focus on supporting Katie, too.

Do you discuss your concerns or beliefs with Katie and the medical team?

When the question comes, “Are there any questions?” I feel like it’s always open for me to chip in, and if it’s not open, I just chip in. I don’t think it’s often asked specifically to the caregiver, or in my experience, a lot of the time not. It’s normally to the patient, what are the patient’s questions, and the caregiver has to take that backseat while the patient goes through a lot of personal things that are going on with them. It’s very much related to the patient. But I do have a lot of questions, I have an analytical mind. I think what Ivy said is true, sometimes there can be a lot of information. Even as a caregiver, and I like to think I’m very detailed, I miss things as well, so it’s great to have that support. We both talk about what happens after meetings as well.

Do you feel like you have enough support as a caregiver, and as a medical field, do you think we could do better in supporting caregivers?

I don’t feel that supported by the medical field, to be honest. There’s a charitable organization, First Descents, that has helped support caregivers who are part of that charity. Getting people outdoors and living in the outdoors is very much a part of what they do. They had a caregiver “Rock program,” they called it, where we went rock climbing with 16 other caregivers from multiple different cancer diagnoses and treatments and where their partners were. For caregivers, that was a very big resource. But I don’t think, in the medical field, I’ve ever had anyone say, “How are you really doing; what resources can we offer to you?” Even when we recently had TIL [tumor-infiltrating lymphocyte] treatment, there wasn’t too much of a focus on the caregiver. I think that’s something that needs to be developed because we do have an impact on helping the patient, and we’re going through a lot at the same time. Helping us to be in a better situation to help the patient really helps.

I always go back to Kate’s diagnosis for brain cancer when it metastasized, and I was telling her, “Oh, you’re probably just dehydrated.” I didn’t think there could be other scenarios going on and feel quite guilty about that. Perhaps if I was educated more, it would have been like, “Well, maybe we should check in with your doctor.” We should report this to your doctor earlier than having to wait for the week after, and then go do the scan and then the doctor says, “Actually, there could be an issue here.” I think there’s a lot of room to help caregivers to be a better support function to patients. I try my best now to advocate after we just had TIL and say, “Maybe you should report that to your doctor. Have you told your doctor about that?” I think stating those expectations and talking openly with a caregiver very much benefits us and also makes us feel heard and valued at the same time.

Thanks so much for sharing that, being so open about that. I think what resonates here is that number one, we do need to do better in supporting caregivers and there needs to be more resources. There is, I think, more interest in that in the field, which is important. Even now, there are data coming out during COVID-19 [coronavirus disease 2019], that there’s a lot of caregiver burnout, caregiver fatigue, and not enough resources. I do think you highlight something that’s really important. The other thing you highlighted is that we need to be better about educating not just patients, but their caregivers, about what kind of things to look out for, and how to best help patients. Thank you for sharing that with us.

Manmeet Ahluwalia, MD, Cleveland Clinic

Delving Into Brain Cancer Treatment Takeaways Following ASCO 2025

Improving Outcomes for Patients With Brain Metastases

A Caregiver’s Perspective on Treatment Success

Feeling Supported During the Diagnosis and Treatment of Brain Metastases

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